Diabetes mellitus is characterized by a broad array of physiologic and anatomic abnormalities, for example, altered glucose disposition, hypertension, retinopathy, abnormal platelet activity, aberrations involving large, medium and small sized vessels, and other problems encountered in diabetic patients. Diabetes is classified into two categories: primary and secondary. Primary diabetes includes: 1) Insulin-dependent diabetes mellitus (IDDM, Type 1), 2) Non-insulin-dependent diabetes mellitus (NIDDM), Type 2) including a) Nonobese NIDDM, b) Obese NIDDM and c) Maturity-onset diabetes of the young. Primary diabetes implies that no associated disease is present, while in the secondary diabetes some other identifiable condition causes or allows a diabetic syndrome to develop, for example, 1) Pancreatic disease, 2) Hormonal abnormalities, 3) Drug or chemical induced, 4) Insulin receptor abnormalities, 5) Genetic syndromes and 6) Others.
Insulin dependence in this classification is not equivalent to insulin therapy, but means that the patient is at risk for ketoacidosis in the absence of insulin. It has been suggested that the terms insulin-dependent and non-insulin-dependent describe physiologic states (ketoacidosis-prone and ketoacidosis-resistant, respectively), while the terms Type 1 and Type 2 refer to pathogenetic mechanisms (immune-mediated and non-immune-mediated, respectively). Using this classification, three major forms of primary diabetes are recognized: (1) type 1 insulin-dependent diabetes, (2) type 1 non-insulin-dependent diabetes, and (3) type 2 non-insulin-dependent diabetes.
Secondary forms of diabetes encompass a host of conditions such as pancreatic disease, hormonal abnormalities, genetic syndromes, and others.
Insulin-dependent diabetes mellitus often develops in childhood or adolescence while the onset of NIDDM generally occurs in middle or late life. Patients with NIDDM are usually overweight and constitute 90 to 95 percent of all diabetics. IDDM results from the destruction of beta cells by an autoimmune process that may be precipitated by a viral infection. NIDDM is characterized by a gradual decline in beta cell function and varying degrees of peripheral resistance to insulin. The annual incidence of IDDM ranges from 10 cases per 100,000 persons for nonwhite males to 16 cases per 100,000 persons for white males. LaPorte, R. E. et al., 1981, Diabetes 30: 279. The prevalence of NIDDM increases with age, especially after age 45 and is higher among blacks than whites and certain populations such as Asian Indians living in South Africa and England. Malter, H. M. et al., 1985, Br. Med. J. 291: 1081. Gestational diabetes occurs in 2.4 percent of all pregnancies in the United States annually. Freinkel, N. et al., 1985, N. Engl. J. Med. 313: 96. Pregnancy is also a state of insulin resistance. This insulin resistance is exacerbated in gestational diabetes which may predispose patients to the various hypertensive syndromes of pregnancy associated with Type 2 NIDDM. Bardicef, M. et al., 1995, Am. J. Gynecol. 172: 1009-1013.
Current therapies for IDDM include insulin therapy, and for NIDDM will include dietary modification in a patient who is overweight and hypoglycemic agents, e.g., tolbutamide, chlorpropamide, acetohexamide, tolazamide, glipizide and glyburide, all of which act by stimulating the release of insulin from the beta cells. Also, thiazolidone drugs like rosiglitazone are being used to treat insulin resistance.
Insulin resistance and hyperuricemia are considered a part of the ‘metabolic syndrome’ or ‘syndrome X’ of obesity, insulin resistance, hypertriglyceridemia and hyperuricemia, which underlies the pathogenesis of type II diabetes. Insulin resistance is an impaired metabolic response to our body's own insulin so that active muscle cells cannot take up glucose as easily as they should. The condition can exist unrecognized and metabolic damage can occur before a full blown Type 2 diabetes is finally diagnosed. Insulin resistant diabetics are 2-5 times more likely to die from heart attack or stroke than are non diabetics. Currently metabolic syndrome is epidemic both in the United States and throughout the world, resulting in exponential increases in health care cost and causing great morbidity and mortality due to the increased risk for cardiovascular and renal disease in this population. Most studies suggest that the epidemic is due to the adaptation of ‘Westernized diet’—this diet is also known to increase our risk for gout (Johnson R J, Rideout B: Uric acid and diet: insights into the Epidemic of Cardiovascular Disease. N Engl J Med (editorial) 2004; 350:1071-1074).
It has widely been assumed that the rise in serum uric acid associated with insulin resistance is due to the effect of insulin to increase urate reabsorption in the renal tubule, and hence it had been assumed that the hyperuricemia associated with insulin resistance does not have a causal role in the syndrome.